CML Treatment Considerations in the Community Setting
Last Updated: Friday, November 12, 2021
Sarah Worth, PharmD, BCOP, BCPS, and Allison Strider, MSN, AGNP-BC, AOCNP, discuss considerations for treating CML in the community setting, including coordinating patient care, staying up to date with the latest treatment guidelines and recommendations, and referring patients to specialists, including cardiology or high-risk OB/GYN, to ensure comprehensive care and the best outcomes.
Meet the faculty
PharmD, BCOP, BCPS
University of Alabama at Birmingham
Sarah Worth is the Leukemia Clinic pharmacist at The Kirklin Clinic of UAB Hospital. In this role, she works with patients with hematologic cancers, including CML patients, providing education when they begin treatment and helping monitor them for adherence and toxicity.
MSN, AGNP-BC, AOCNP
University of Alabama at Birmingham
Allison Strider is a nurse practitioner within the Infusion Services at The Kirklin Clinic of UAB Hospital, specializing in assessing and treating patients with chemotherapy and immunotherapy adverse effects, as well as educating patients, caregivers, and other staff.
Chronic myeloid leukemia (CML) has become more of a chronic disease, with longer survival among patients taking tyrosine kinase inhibitors, also known as TKIs.1 It is essential that hematology/oncology providers recognize the importance of identifying current health conditions and coordinating care with other providers in the patient’s care team, such as a general practitioner, cardiologist, pulmonologist, OB/GYN, and others as necessary. Community care providers are key in connecting these and helping the patients coordinate the care needed.
This is especially important because CML is often diagnosed and managed in the community. APPs and other providers need to understand the most recent guidelines when diagnosing CML, whether in chronic or advanced phase, and stay up to date with the available treatments and adverse effect profiles. NCCN Guidelines are a comprehensive and fantastic resource for this.2
At diagnosis, these guidelines recommend that patients receive a complete workup, including a bone marrow biopsy and cytogenetic testing.2 A quantitative RT-PCR (qPCR) using the International Scale (IS) for BCR-ABL1 should be taken with baseline labs to check for atypical BCR-ABL1 transcripts. If a rare or atypical BCR-ABL1 transcript is detected, we can consider a referral to a CML specialist.2 Any rare hematologic malignancies should be referred to a specialty center for further workup and treatment initiation.2 Community providers should consider a similar referral if CML is found in an advanced stage, either accelerated or blast phase, for evaluation for allogeneic hematopoietic cell transplantation (HCT). If CML is diagnosed in an accelerated phase, consider adding a myeloid mutation panel and adding flow cytometry as well.2
Yes, the diagnosis of CML is a critical time to recognize what resources and referrals each patient may need, as well as to identify any comorbidities the patient has that could impact treatment choices. Providers in the community may have less access to specialists but are often the first to see these high-risk patients. It’s important to identify the patients that need specialty referrals and are able to work within a collaborative team to get this accomplished.
An example of this is when CML presents in a woman who is pregnant. This woman should be referred to a CML specialist and high-risk OB/GYN within the same institution because TKIs—the primary treatment for CML—are contraindicated during pregnancy and breastfeeding.2 After delivery, she can transition to her local oncologist for TKI therapy if she wishes.
We’ve seen this specific example at our institution. Another important specialty referral is cardiology. Some institutions, including ours, has a specialty cardio-oncology team available. But in the community setting, this may not be available. So you may try collaborating with a cardiologist who is willing to learn the special adverse effect profiles of some of these TKIs. If not, the increased surveillance may fall on the APP or other oncology provider.
In the last several years, comprehensive guidelines have been released on how to best evaluate for cardiac risk factors, both modifiable and nonmodifiable, and how to monitor for cardiac and vascular toxicities throughout TKI treatment.3 We should always complete a baseline cardiac assessment with blood pressure reading, regardless of which TKI therapy the patient is receiving.3 Then the remainder of the testing and its frequency depends on the patient’s health history, current comorbid conditions, and which TKI therapy is to be started.3 There are also available guidelines for hyperlipidemia and hyperglycemia, which are most commonly seen with nilotinib but can be seen with ponatinib as well.3
It is definitely important to establish all of these baseline values before starting treatment with these particular TKI medications. As an example, if you have a patient with high-risk CP-CML and a cardiac comorbidity such as heart failure or QT prolongation, you may consider a second-generation TKI like bosutinib. If possible, you should conduct an initial screening with a cardio-oncologist. If that’s not available at your institution, collaborate closely with the patient’s cardiologist to have the initial screening completed before the TKI is started. Since bosutinib may cause diarrhea, monitor your patient’s fluid status and electrolytes closely to offer supportive care.4 Ensure cardiology follows up every 3 to 6 months and more often if clinically indicated.3,4
In addition to a cardiologist, a dedicated oncology pharmacist can be an asset to an integrative care team. They can help tremendously with these potential interactions between TKIs and other medications. Also, each TKI has a particular way it must be taken to ensure absorption, which can sometimes be difficult for patients to follow.4 For example, imatinib is best taken with a large meal and a full glass of water, whereas nilotinib must be taken on an empty stomach, with patients avoiding food 2 hours before and 1 hour after taking the medication.5,6 An oncology pharmacist can educate patients to ensure they understand these instructions and have the best outcomes. Not all practices may have a clinic pharmacist, but specialty pharmacies offer initial education and can assist with follow-up of patients as well. Additionally, programs offered by manufacturers can also serve as resources for patients.
It’s also vital to include either a financial counselor or social worker on the team to assist patients who are uninsured or underinsured. Our pharmacy and most specialty pharmacies assist with enrolling patients in grants if available. In cases where a patient can’t afford certain medications, social workers, nurses, or other clinic staff may play a big role in assisting these patients with applications for manufacturer assistance, in addition to other resources, to pay for labs and clinic visits.
I definitely agree, Sarah. The goal is to provide support for the patient and family members so they have the best chance of getting their CML under control. To do this, it is important to monitor their BCR-ABL1 closely as indicated by the NCCN Guidelines.2 In a study published by Goldberg et al. (2017), close monitoring of patients with CML was more likely to be done by academic centers versus community practices.7 This can be due to fewer providers, less access to specialty testing, or patients with limited resources to travel to clinic visits. The goal of TKI therapy in CML is disease control and improved quality of life, which can be achieved by aggressive monitoring and adherence to their TKI. The long-term goals will differ depending on the patient, and certain patients will need allogeneic HCT or be eligible for consideration of TKI discontinuation.2 However, if patients are unable to enter a successful treatment-free remission, they will likely need lifelong TKI therapy.
Those patients who have been maintained and have documented deep molecular response for at least 3 years on the same therapy can be considered for TKI discontinuation. More recent data has shown that sustaining this response for at least 6 years correlates with improved responses.2 We start discussing this as early as diagnosis with some patients, but the goal is to keep them on TKI therapy with a sustained deep molecular response before discontinuing so they have the best chance of staying off therapy.2 To qualify for TKI discontinuation, they must meet strict criteria and agree to frequent monitoring for at least the first year. It is highly recommended to either consult with a CML specialist or refer the patient to a specialty center to understand the potential risks and benefits of TKI discontinuation, including the signs and symptoms of withdrawal syndrome.2
These are important points. In the end, it is important that community oncology providers are able to identify the needs of the patient, collaborate with other specialty providers, and make referrals as needed. They should utilize their available resources, such as oncology pharmacists, social workers, and financial counselors to help ensure adherence, affordability, and proper monitoring.
- Cuellar S, Vozniak M, Rhodes J, et al. BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia. J Oncol Pharm Pract. 2018;24:433-452.
- Deininger MW, Shah NP, Altman JK, et al. Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18:1385-1415.
- Medeiros BC, Possick J, Fradley M. Cardiovascular, pulmonary, and metabolic toxicities complicating tyrosine kinase inhibitor therapy in chronic myeloid leukemia: Strategies for monitoring, detecting, and managing. Blood Rev. 2018;32:289-299.
- Bosutinib prescribing information. Approved 2012. Accessed August 12, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203341s009lbl.pdf
- Imatinib prescribing information. Approved 2001. Accessed August 12, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021588s024lbl.pdf
- Nilotinib prescribing information. Approved 2007. Accessed August 12, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022068lbl.pdf
- Goldberg SL, Cortes JE, Gambacorti-Passerini C, et al. First-line treatment selection and early monitoring patterns in chronic phase-chronic myeloid leukemia in routine clinical practice: SIMPLICITY. Am J Hematol. 2017;92:1214-1223.